1. Field of the Invention
This invention relates to new semi-synthetic aminoglycosidic antibiotics, including a 1-N-[.alpha.-hydroxy-.omega.-aminoalkanoyl]-5,3',4'-trideoxykanamycin B; 1-N-[.alpha.-hydroxy-.omega.-aminoalkanoyl]-5,3',4',6"-tetradeoxykanamycin B and 5,3',4',6"-tetradeoxykanamycin B as well as a 1-N-[.alpha.-hydroxy-.omega.-aminoalkanoyl]-5,3',4'-trideoxy-6'-N-methylka namycin B and 5,3',4'-trideoxy-6'-N-methylkanamycin B which are each the new compound useful as antibacterial agent. This invention also relates to processes for the production of these new compounds. This invention further relates to an antibacterial composition comprising one of these new compounds as the active ingredient.
2. Description of the Prior Art
Dibekacin, namely 3',4'-dideoxykanamycin B was semi-synthetically produced from kanamycin B by the present inventors (see Japanese patent publication No. 7595/75; Japanese patent No. 794,612; U.S. Pat. No. 3,753,973). Dibekacin has been used extensively in therapeutic treatment of various bacterial infections as a chemotherapeutic agent which is active against the kanamycin-sensitive bacteria and also against various kanamycin-resistant bacteria. We, the present inventors, produced semi-synthetically habekacin, namely 1-N-(L-4-amino-2-hydroxybutyryl)-dibekacin which is a chemotherapeutic agent effective against dibekacin-resistant bacteria (see Japanese patent publication No. 33,629/77; U.S. Pat. No. 4,107,424). We also produced semi-synthetically a 1-N-[.alpha.-hydroxy-.omega.-aminoalkanoyl]-6'-N-methyldibekacin which has been found to be highly active against various strains of bacteria (Japanese patent application No. 115199/74; U.K. Pat. No. 1,475,481; U.S. Pat. No. 4,147,861). In our further researches, we produced synthetically the 6"-deoxy or 4",6"-dideoxy derivatives of dibekacin and habekacin, i.e., 1-N-(L-4-amino-2-hydroxybutyryl)-dibekacin, respectively. Furthermore, we have found that these 6"-deoxy derivatives and 4",6"-dideoxy derivatives of dibekacin or habekacin exhibit not only a low oto-toxicity but also show an antibacterial activity as high as that of dibekacin or habekacin (see Japanese patent application No. 119323/79; U.K. patent application GB 2 058 774 A and U.S. patent application Ser. No. 174,630), now U.S. Pat. No. 4,332,794.
We also produced 5,3',4'-trideoxykanamycin B as a further deoxy derivative of dibekacin (Japanese Journal of Antibiotics, 32, S-178, (1979)). However, it has been found that 5,3',4'-trideoxykanamycin B is less active than dibekacin.
It may be added that we further have produced some deoxy derivatives of 1-N-(L-4-amino-2-hydroxybutyryl)kanamycin A (ie. amikacin), including 3'-deoxyamikacin (Japanese patent application No. 49105/75; U.S. Pat. No. 4,104,372), 3',4'-dideoxyamikacin (Japanese patent application No. 11402/79; U.K. patent application No. GB 2043 034 A, U.S. patent application Ser. No. 114,779 now U.S Pat. No. 4,298,727); 6"-deoxyamikacin (Japanese patent application No. 54733/79); 4",6"-dideoxyamikacin (Japanese patent application No. 54733/79); 3',4',4",6"-tetradeoxyamikacin (Japanese patent application No. 138685/79) and 3',4',6"-trideoxyamikacin (Japanese patent application No. 5657/80), as well as 3',6"-dideoxyamikacin; 5,3'-dideoxyamikacin and 5,3',6"-trideoxyamikacin (Japanese patent application No. 107202/80) which all have a low acute toxicity and a low oto-toxicity with exhibiting a useful antibacterial activity as high as that of amikacin.